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Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.

Kos K, Wong S, Tan B, Gummesson A, Jernas M, Franck N, Kerrigan D, Nystrom FH, Carlsson LM, Randeva HS, Pinkney JH, Wilding JP - Diabetes (2009)

Bottom Line: Adipose tissue collagen has recently been found to be linked with metabolic dysregulation.In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.

ABSTRACT

Objective: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines.

Research design and methods: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses.

Results: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.

Conclusions: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.

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Related in: MedlinePlus

SPARC during VLCD 16-week 450 kcal/day in subjects with (METS+) and without (METS−) the metabolic syndrome. Data from SPARC adipose tissue expression of subjects of both groups were compared with their baseline levels (top) and the within-patient variation with the previous time point. R, refeeding; W, week. **P < 0.01, ***P < 0.001, n = 24.
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Figure 3: SPARC during VLCD 16-week 450 kcal/day in subjects with (METS+) and without (METS−) the metabolic syndrome. Data from SPARC adipose tissue expression of subjects of both groups were compared with their baseline levels (top) and the within-patient variation with the previous time point. R, refeeding; W, week. **P < 0.01, ***P < 0.001, n = 24.

Mentions: Obese subjects in the VLCD study lost 18 kg in the first 8 weeks and an additional 10 kg by week 16. There was no further weight loss from week 16 to 18. The average SPARC expression in the adipose tissue of these subjects decreased by 33% in the first 8 weeks (P < 0.0001, paired t test). However, despite further weight loss, there was no change in SPARC expression between 8 and 16 weeks (P = 0.74, paired t test). Between 16 and 18 weeks, during which period the subjects went from VLCD to regular food while remaining weight stable, the SPARC expression increased significantly (20% rise, P < 0.0001, paired t test) and remained significantly correlated with insulin, glucose, and leptin levels but not adiponectin levels (data not shown). There was no difference in SCAT-SPARC expression in the group with the metabolic syndrome, but there was a tendency to a further decline of SPARC at week 16 (Fig. 3).


Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.

Kos K, Wong S, Tan B, Gummesson A, Jernas M, Franck N, Kerrigan D, Nystrom FH, Carlsson LM, Randeva HS, Pinkney JH, Wilding JP - Diabetes (2009)

SPARC during VLCD 16-week 450 kcal/day in subjects with (METS+) and without (METS−) the metabolic syndrome. Data from SPARC adipose tissue expression of subjects of both groups were compared with their baseline levels (top) and the within-patient variation with the previous time point. R, refeeding; W, week. **P < 0.01, ***P < 0.001, n = 24.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2712789&req=5

Figure 3: SPARC during VLCD 16-week 450 kcal/day in subjects with (METS+) and without (METS−) the metabolic syndrome. Data from SPARC adipose tissue expression of subjects of both groups were compared with their baseline levels (top) and the within-patient variation with the previous time point. R, refeeding; W, week. **P < 0.01, ***P < 0.001, n = 24.
Mentions: Obese subjects in the VLCD study lost 18 kg in the first 8 weeks and an additional 10 kg by week 16. There was no further weight loss from week 16 to 18. The average SPARC expression in the adipose tissue of these subjects decreased by 33% in the first 8 weeks (P < 0.0001, paired t test). However, despite further weight loss, there was no change in SPARC expression between 8 and 16 weeks (P = 0.74, paired t test). Between 16 and 18 weeks, during which period the subjects went from VLCD to regular food while remaining weight stable, the SPARC expression increased significantly (20% rise, P < 0.0001, paired t test) and remained significantly correlated with insulin, glucose, and leptin levels but not adiponectin levels (data not shown). There was no difference in SCAT-SPARC expression in the group with the metabolic syndrome, but there was a tendency to a further decline of SPARC at week 16 (Fig. 3).

Bottom Line: Adipose tissue collagen has recently been found to be linked with metabolic dysregulation.In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.

ABSTRACT

Objective: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines.

Research design and methods: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses.

Results: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein.

Conclusions: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.

Show MeSH
Related in: MedlinePlus